Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis.

The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.     

RESOURCE REVIEWS DEPARTMENT

Book Reviews : RESPIRATORY DISORDERS Susan F. Wilson & June M. Thompson Book Reviews : PROCEEDINGS FROM THE FIRST COLLOQUIUM ON PREVENTING SECONDARY DISABILITIES AMONG PEOPLE WITH SPINAL CORD INJURY Philip L. Graitcer & Frederick M. Maynard (Eds.) Book Reviews : KRUSEN'S HANDBOOK OF PHYSICAL MEDICINE AND REHABILITATION (4th ed.) Frederick J. Kottke & Justus F. Lehmann (Eds.) Book Reviews : PSYCHOLOGICAL MANAGEMENT OF TRAUMATIC BRAIN INJURIES IN CHILDREN AND ADOLESCENTS Ellen Lehr Book Reviews : TRAUMA, TRANSFORMATION, AND HEALING John P. Wilson, Brunner/Mazel Book Reviews : REHABILITATION AND DISABILITY: PSYCHOSOCIAL CASE STUDIES E. Davis Martin, Jr., & Gerald L. Gandy, Charles C. Thomas     

A data adaptive reprojection technique for MR angiography.

Inability to detect vessel overlap and vascular loops can compromise the interpretation of magnetic resonance angiograms. A data-adaptive ray tracing (DART) technique was developed to produce the appropriate variations in signal intensity at points of vessel overlap in order to simulate the standard angiographic representation of vessels. In this technique a threshold is utilized to identify vessels in the image slices composing a 3D angiographic data set. A mask, which defines regions slightly larger than the vessel boundaries, is obtained by blurring the vessel information surviving the initial threshold. This mask is converted to binary form prior to multiplication by the original angiographic data set. Following application of an additional threshold to the masked data, line integrals through the regions defined by the mask are performed to obtain an angiographic signal proportional to the integrated vessel signal as in conventional angiography. This integrated reprojection is then uniquely combined with a maximum intensity pixel (MIP) reprojection to produce the final DART image. The application of the DART technique to 2D time-of-flight and 3D phase-contrast angiograms successfully enabled the identification of over-lapping vessels and vascular loops. DART was also found to produce less vessel narrowing than the MIP technique.     

Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis.

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases. By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn's disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener's granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes.     

Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature,primary amenorrhea,unilateral gonadoblastoma,and a 46,X,del(Y)(q11)/45,X karyotype

Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM‐mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley‐Liss, Inc.     

Effects of tennis training on lipid metabolism and lipoproteins in recreational players.

OBJECTIVE: To investigate the short term effects of tennis training on lipid metabolism and to find out if a typical tennis training programme has positive longitudinal effects on cardiovascular risk factors in recreational players. METHODS: The experimental design consisted of an exercise study and a subsequent longitudinal study. In the exercise study the short term metabolic effects of a two hour technically orientated tennis training (TT) session and a running intensive tennis training (RIT) session were investigated in 16 recreational tennis players (eight men: 46 (SD 7) years, 177 (6) cm, 81 (10) kg; and eight women: 44 (5) years, 165 (5) cm, 64 (6) kg). In the longitudinal study the long term effects of a six week RIT programme in 22 players (11 men and 11 women) of similar characteristics were compared with those in 16 control subjects (eight men and eight women). The results of the exercise study (higher lipolytic activity and cardiopulmonary demand, as well as acceptance by the players) led to the RIT method being chosen for all training sessions in the longitudinal study. RESULTS: In RIT, significantly higher values for heart rate (148 (SD 10) v 124 (11) beats/minute) and lactate (2.8 (1.1) v 1.5 (0.6) mmol/l), significantly higher post exercise concentrations of serum glycerol (0.37 (0.15) v 0.29 (0.14) mmol/l) and high density lipoprotein cholesterol (1.31 (0.55) v 1.20 (0.50) mmol/l) and a higher acceptance than in TT (15 of the 16 players preferred RIT) were found. During the six week tennis training programme the changes in body weight (-1.41 (1.56) v 0.00 (1.50) kg) and anaerobic threshold (1.04 (0.84) v -0.08 (0.92) km/h) were significantly different between the training and control group. In the training group several parameters of the lipoprotein profile tended to change in an antiatherosclerotic direction. CONCLUSIONS: The results indicate that typical regular tennis training influences cardiovascular risk factors in a positive manner and can be suggested as an attractive alternative to other current health orientated sports programmes. A more frequent use of running intensive exercises during tennis training is recommended.     

The structure of wandering in dementia

‘Wandering’ is one of the most troublesome of behavioural problems in dementia. The term ‘wandering’ covers many different types of behaviour. We examined the hypothesis that the different types of wandering behaviour seen in dementia from a scale using data collected on 83 elderly subjects suffering from either Alzheimer's disease or multiinfarct dementia. We reject the scaling hypothesis. Our data suggest that there are three main categories of wandering behaviour, and that one of these categories is usefully divided into four subcategories.     

Methylmercury poisoning: Long-term clinical,radiological, toxicological,and pathological studies of an affected family

For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and atentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retradation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage.     

Calming an Escalated Psychiatric Milieu

On inpatient psychiatric units, nurses control the tone, pace, and activity level of the environment. But under the influence of factors such as high patient acuity and negative group contagion, a milieu can become unacceptably loud and chaotic. A volatile milieu is a potentially dangerous environment because patients' anxiety and agitation can quickly lead to acting out and aggression. This article focuses on how nurses can regain control of a milieu spiralling into chaos by tightening the structure of the routine, anticipating potential problems, and maintaining a confident calm manner. The charge nurse orchestrates the staff group's response to escalation through detailed planning, decisive interventions, and strategic use of every available resource.